The recently developed techniques of MRI (magnetic resonance imaging) or NMR (nuclear magnetic resonance) imaging encompasses the detection of certain atomic nuclei utilizig magnetic fields and radio-frequency radiation. It is similar in some respect to X-ray computed tomography (CT) in providing a cross-sectional display of the body organ anatomy with excellent resolution of soft tissue detail. In current use, the images produced constitute a map of the distribution density of protons and/or their relaxation times in organs and tissues. The MRI technique is advantageously non-invasive as it avoids the use of ionizing radiation.
While the phenomenon of NMR was discovered in 1945, it is only relatively recently that it has found application as a means of mapping the internal structure of the body as a result of the original suggestion of Lauterbur (Nature, 242, 190-191, 1973). The lack of any known hazard associated with the level of the magnetic and radio-frequency fields that are employed renders it possible to make repeated scans on vulnerable individuals. Additionally, any scan plane can readily be selected including transverse, coronal, and sagittal sections.
In an NMR experiment, the nuclei under study in a sample (e.g. protons) are irradiated with the appropriate radio-frequency (RF) energy in a highly uniform magnetic field. These nuclei, as they relax, subsequently emit RF radiation at a sharp resonant frequency. The emitted frequency (RF) of the nuclei depends on the applied magnetic field.
According to known principles, nuclei with appropriate spin when placed in an applied magnetic field [B, expressed generally in units of gauss or tesla (10&lt;4&gt;gauss)] align in the direction of the field. In the case of protons, these nuclei precess at a frequency f=42.6 MHz at a field strength of 1 Tesla. At this frequency, an RF pulse of radiation will excite the nuclei and can be considered to tip the nuclei out of the field direction, the extent of this rotation being determined by the pulse duration and energy. After the RF pulse, the nuclei "relax" or return to equilibrium with the magnetic field, emitting radiation at the resonant frequency. The decay of the signal is characterized by two relaxation times, i.e., T1, the spin-lattice relaxation time or longitudinal relaxation time, that is, time taken by the nuclei to return to equilibrium along the direction of the externally applied magnetic field, and T2, the spin-spin relaxation time associated with the dephasing of the initially coherent precession of individual proton spins. These relaxation times have been established for various fluids, organs and tissues in different species of mammals.
In MRI, scanning planes and slice thickness can be selected without loss of resolution. This permits high quality transverse, coronal and sagittal images to be obtained directly. The absence of any moving parts in MRI equipment promotes a high reliability. It is believed that MRI or NMR imaging has a greater potential than CT for the selective examination of tissue characteristics in view of the fact that in CT, X-ray attenuation coefficients alone determine image contrast, whereas at least four separate variables (T1, T2, nuclear spin density and flow) may contribute to the NMR signal. For example, it has been show (Damadian, Science, Vol. 171, p. 1151, 1971) that the values of the T1 and T2 relaxation in tissues are generally longer by about a factor of 2 in excised specimens of neoplastic tissue compared with the host tissue.
By reason of its sensitivity to subtle physio-chemical differences between organs and/or tissues, it is believed that MRI may be capable of differentiating tissue types and in detecting diseases which induce physio-chemical changes that may not be detected by X-ray or CT which are only sensitive to differences in the electron density of tissue. The images obtainable by MRI techniques also enable the physician to detect structures smaller than those detectable by CT and thereby provide comparable or better spatial resolution.
The use of perfluorocarbon compounds in various diagnostic imaging technologies such as ultrasound, magnetic resonance, radiography and computed tomography, has been set forth in an article by Robert F. Mattrey in SPIE, Volume 626, Medicine, XIV/PACS IV (1986), pages 18-23.
Magnetic resonance imaging of liver tumor in rats using perfluorochemical emulsions was reported in "In Vivo .sup.19 F NMR Imaging of Liver, Tumor and Abcess in Rats", H. E. Longmaid III, et al., INVESTIGATIVE RADIOLOGY, March-April 1985, Vol. 20, p. 141-144. The compounds utilized displayed multiple peak NMR spectra.
Imaging of brain tumors with perfluorooctyl bromide has been described in "Brain-Tumor Imaging Using Radiopaque Perfluorocarbon", Nicholas J. Patronas, M.D., et al. JOURNAL OF NEUROSURGERY, May 1983, Vol. 58, pp. 650-653.
Ultrasound imaging of organs has been enhanced by FLUOSOL-DA (perfluorodecalin and perfluorotripropylamine) as reported in "Perfluorochemicals as US Contrast Agents for Tumor Imaging and Hepatosplenography: Preliminary Clinical Results", Robert F. Mattrey, M.D., et al., RADIOLOGY, May 1987, Vol. 163, No. 2, pp. 339-343.
In European published Patent Application 0 118 281, published September 12, 1984, a technique for the detection of gas in an animal is set forth using nuclear magnetic resonance techniques embodying various fluorochemical agents. Among the fluorochemical agents there is included perfluoroether polymer (Fomblin Y/01).
In U.S. Pat. No. 4,523,039 the production of fluorocarbon ethers of various structures is set forth wherein the resulting fluorocarbon ether produces a noncyclic structure.
U.S. Pat. No. 4,570,004 describes a method of production and a composition of matter including perfluoro 15-crown-5 ether. The patent identifies that the crown ethers in general can be useful as oxygen carriers and various biomedical products.
U.S. Pat. No. 4,639,364 discloses the use of various fluorine-containing compounds for magnetic resonance imaging.
The prior art, despite its suggestion for the use of magnetic resonance imaging for medical and biodiagnostic purposes and the prior art's suggestion of various fluorine-containing compounds for use as agents in nuclear magnetic resonance imaging, has failed to provide a particularly sensitive fluorine agent for nuclear magnetic resonance imaging which provides high signal to noise ratios sufficient for detailed diagnosis of deep tissue structures and fine resolution requirements.